An antihistamine "gestalt and a method for preventing allergological young farm animals

 

(57) Abstract:

Usage: for non-specific immunostimulating prevention allergological young farm animals: edematous disease of pigs, pneumoenteritis calves, etc., the inventive historic contains mg/ml: histamine 0,00005 - 0,0001; a copolymer of vinylpyrrolidone with an organic acid as a carrier 0,00154-0,0611 and the solvent else. As the solvent, the product contains saline solution or a mixture of saline solution and oil adjuvant at a ratio of 1:1, or a mixture of saline and 3-5% aqueous suspension of silicon dioxide in a ratio of 1: 1. Historic resulting from conjugation of histamine with the level of organic acid in the composition of the copolymer with vinyl pyrrolidone. To prevent allergological historic injected animals intramuscularly: pigs for 7-10 days. up to weaning in the volume of 1-2 ml after a single dose, twice: for 14-20 days before weaning with an interval of 6-8 days. in a volume of 1-2 ml per injection; calves on the first day of life in a volume of 2-3 ml of the Invention allows to increase the stability of the composition and properties of the drug and the effectiveness of prevention allergological and snegoriy and can be used for non-specific immunostimulating prevention allergological young farm animals: edematous disease of pigs, pneumoenteritis calves, etc.

Industrial management livestock breeding animals on productivity, standardize them by breed, sex and age, as well as a large concentration of livestock in the livestock premises lead to the occurrence of animal diseases such as disease, crowding, disease concentration" or "factor of infection". At the core of most of these diseases are allergenicity associated with the violation of the regime and diet, stress, hypokinesia, etc. Multiple etiological factors for these diseases is not possible in the conditions of the economy to draw a clear boundary between non-infectious and infectious diseases, making it difficult to maintain effective therapy and prophylaxis. These multifactorial diseases include edema disease of swine, pneumoenteritis calves (neuralgia, pneumonia), etc.

Despite numerous studies conducted by scientists in different countries, the nature of the edema disease is still not fully disclosed. Some consider specific pathogen her beta-hemolytic strains of Escherichia coli of different serotypes, other intestinal cholerae, third coccal flora, the fourth assertion is. Some include edema disease in a group of avitaminosis Century, the Lack of a unified perspective on the etiology of the disease makes it difficult to develop effective measures against it [1]

However, the analysis of the literature suggests that edema disease of swine that non-communicable, acute or subacute disease characterized by lesions of the Central nervous system and gastrointestinal tract, acute heart failure and the presence of gelatinous edema in the tissues. The pathogenic nature of this disease is allergologists. Essential in its development have impaired the regulation of immune responses of the gut and the interaction of the immune system of the gastrointestinal tract aft antibodies. In the occurrence of edema disease plays a decisive role dysbacteriosis of the intestine, characterized by a sharp decrease in the number of normal microflora and the rapid multiplication of beta-hemolytic Escherichia coli, hemolytic cocci and staphylococci on the background of the food Allergy and various adverse factors that reduce the body's resistance. The impetus for the emergence edematous disease, along with such stress factors as transportation, vaccination, cm is 2">

The leading factor in the development of edema syndrome is a histamine intoxication due to excessive accumulation in the body in the bacterial decarboxylation of histidine for intestinal dysbiosis, which is the main cause of hemodynamic disorders and death of pigs from collapse or shock.

The disease affects pigs of all age groups, but most often piglets during weaning. The duration of the disease varies from a few hours to several days. The incidence of more than 40% mortality can reach 100% [2]

For the prevention and treatment of edema disease of swine known to use various antibiotics, chemotherapeutic and biological products (immune sera, vaccines) both separately and in combination.

To suppress toxigenic microflora in the intestine inside designate neomycin, monomitsin, polymyxin, chlortetracycline, chloramphenicol, and other antibiotics in the dose of 0.015-0.02 g/kg 2-3 times a day for three consecutive days. The antibiotics chosen by Podarok.

It is also known the use of sulfadimesine, sulfadimethoxine oral dose of 1 g and furazolidone dose of 0.25 g per animal 2-3 times a day during the and at a dose of 15-20 ml

Obviously sick pigs with signs of enterotoxaemia, in addition to the above drugs, injected subcutaneously kordiamin at a dose of 0.07 ml/kg 2-3 times a day until complete disappearance of symptoms of cardiovascular disease and improve the overall condition of the animals, intramuscularly, vitamin b1at a dose of 10-20 mg/animal,12at a dose of 30-50 mg/animal once a day 3-4 bottoms in a row.

At the final stage of preventive therapy after cessation of giving antibiotics to all piglets to weaning, give acidophilus preparations [1]

Disadvantages of these methods of prevention and treatment of edema disease of swine are that with long-term use of antibiotics or sulfa drugs, you may experience resistant to races of microbes, development of dysbiosis, side effects toksikoallergicheskie character.

Good therapeutic and preventive effect when edematous disease have acidophilus drugs recommended by Professor F. F. Powder in 1960, However, limited their production holds wide application.

Attempts have been made use of vaccines for the prevention of edema disease, but had no success due to G proteins [3]

In the mechanism of the disease is an important role for active biogenic amines and primarily histamine. For reducing the amount of histamine in the body of pigs with edema disease used antihistamines, enhancing the natural resistance of the organism. This purpose is recommended to enter the piglets before and after weaning intramuscularly 5% solution orally as tablets in a dose of 1 ml/kg of body weight. As desensitizing means prescribed diphenhydramine, pipolphen, promethazine etc.

However, wide use of them in veterinary practice prevent side effects, addictive. In addition, when repeated injections they cause allergic reactions [4]

The closest to the invention by the combination of essential features is an antihistamine of listglobal, including gamma globulin as a carrier, histamine and saline solution in the following ratio of components, mg/ml:

Gamma globulin 4 8

Histamine 0,00005 0,0001

Saline Else

When mixing of histamine with gamma globulin antigenic complex is formed, against which the body produces protective antibodies. Proactive e is e time will neutralize the harmful effects of excess histamine [5]

The main disadvantages of gitagovinda are as follows:

it contains gamma globulin is a bad standard drug, because of its quality and biological activity depend on which allocation method: precipitation with alcohol, rivanol or polyethylene glycol, which reduces the prophylactic effect of gitagovinda;

complex formation of histamine-gamma-globulin is not accompanied by the creation of covalent bonds between them, which leads to instability of the composition and properties of the drug and reduce the preventive effect of its use.

Also known a method for preventing allergological young farm animals through the use of antihistamine drug gitagovinda of the following composition (mg/ml:

Histamine 0,00005-0,0001

Gamma globulin 4 8

Saline Else,

which is injected to the animals subcutaneously in the week prior to weaning at doses of 2 ml three times with an interval of 7 DN [5]

This decision was taken as a prototype.

The disadvantages of the prototype method consist in the fact that it has a high complexity associated with multiple drug animals, and a low of preventive eocytes immunostimulant, standard quality and are suitable for the formation of covalent bonds with histamine, as well as development on its basis of antihistamine drug having a stable composition and properties and higher than gistaglobina preventive effect, and ways to prevent allergological young farm animals, aimed at reducing the complexity of the introduction of antihistamine and increase its prophylactic efficacy.

The problem is solved by the creation of a group of inventions to form a single inventive concept includes a set of essential features that provide technical result in all cases to which the claimed amount of legal protection.

The proposed group of inventions includes an antihistamine and a method for preventing allergological of young farm animals.

An antihistamine (author name "Gestalt") includes the following set of essential features that provide technical result, in all cases, which sought the scope of legal protection:

Histamine 0,00005 0,0001

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An antihistamine "Gestalt" is also characterized by other symptoms, expressing the specific forms of its implementation:

as the carrier of the drug contains a copolymer of vinylpyrrolidone and acrylic acid;

as the carrier of the drug contains a copolymer of vinylpyrrolidone with crotonic acid;

as the solvent, the product contains saline;

as a solvent, the drug contains a mixture of saline solution and oil adjuvant in the ratio of 1:1;

as the solvent, the drug contains a mixture of saline and 3 5% aqueous suspension of silicon dioxide in a ratio of 1:1.

Features of the invention, characterizing an antihistamine and coinciding with the characteristics of the prototype, including a generic term that reflects the assignment are:

an antihistamine, which includes:

histamine;

media histamine;

the solvent.

Compared with the prototype the main feature of the invention is the inclusion of vistalite as a carrier of a copolymer of vinylpyrrolidone with an organic acid.

Other distinctive prismacolored copolymer of vinylpyrrolidone and acrylic acid;

as the carrier of the drug contains a copolymer of vinylpyrrolidone with crotonic acid;

as the solvent, the product contains saline;

as a solvent, the drug contains a mixture of saline solution and oil adjuvant in the ratio of 1:1;

as the solvent, the drug contains a mixture of saline and 3 5% aqueous suspension of silicon dioxide in a ratio of 1:1.

Copolymer of vinylpyrrolidone with an organic acid, which is used acrylic and crotonic acid, has the following structural formula:

< / BR>
Polymer 1: R-H copolymer of vinylpyrrolidone and acrylic acid.

Polymer 2: R-CH3copolymer of vinylpyrrolidone with crotonic acid.

It is known that these copolymers have adjuvant properties and are used to stimulate the immune response against viral agents [6, 7, 8]

In the invention first proposed to use the polymers 1 and 2 as a carrier for the creation of effective drugs against non-viral disease of young farm animals caused by excessive accumulation in their body histamine, with specified polymer

The functional group of the polymer 1 or 2, reactive against histamine is a carboxyl group of acrylic or crotonic acid. The structural formula of the monomer level, modified by the remainder of histamine, has the following form:

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It should be noted that the term "holder" in relation to gamma globulin used conventionally, since the formation of the complex is not accompanied by the creation of covalent bonds between histamine and protein, whereas in accordance with the invention in the conjugation of histamine with Monomeric link acrylic or crotonic acid composition of the copolymer formed covalent amide bond and high molecular weight polyelectrolyte becomes a carrier for histamine low molecular weight hapten.

The composition used as carriers of polyelectrolytes can be set by mixing different amounts taken for copolymerization of monomer units. The ratio of moles of monomer units in the resulting copolymer determined by chemical methods, it is then possible to calculate the amount of polyelectrolyte required for the conjugation reaction with histamine. Because the reactive part used polyelectrolyte is a group of 2 or 20 mol of acid per 1 mol of histamine. Excess acid must ensure full adherence of histamine to the polyelectrolyte. The number of remaining components of the reaction mixture was calculated based on the number taken histamine: 1 mol of histamine in response was administered to 20 mol of water-soluble carbodiimide and 40 mol of glycine after conjugation.

Testing properties of the conjugate in the experiments on pigs showed that the protective effect in relation edematous disease was higher in the case of the use of the conjugate obtained with a ratio of 1 mol of histamine 2 mol of acid in the composition of the polyelectrolyte. This fact allows us to recognize the aforementioned ratio is optimal.

For conjugation with histamine also suitable are copolymers of vinylpyrrolidone with such derivatives of acrylic or crotonic acid, as they are activated, for example, N hydroxysuccinimide esters. When introduced into the reaction mixture of a copolymer of vinylpyrrolidone with activated ester of the acid does not require the use of water-soluble carbodiimide, but the result is the conjugate of the same composition.

Usually conjugate receive in the form of a concentrate containing 100,000 doses in a volume of 15 ml For the preparation of a specified number in 1 ml of its volume, the conjugate was diluted in different solvents. As a solvent it is proposed to use a saline solution, a mixture of saline solution and oil adjuvant in the ratio of 1:1, or a mixture of saline and 3 5% aqueous suspension of silicon dioxide in a ratio of 1:1.

Know the use of saline as a solvent of medications, including gitagovinda intended for parenteral administration. As solvents complex (physiological) solutions do not have advantages over simple isotonic solutions of sodium chloride or glucose [5, 9]

Know the use of oil adjuvants in the manufacture of emulsion vaccines. Adjuvant provide distinct immunological stimulation by mixing them with water-dissolved antigen and obtaining a water-oil emulsion. As the base oil adjuvant know the use of oils of different origin: Bailleul F, draker 6VR, marcol 52, liquid paraffin, perfume, vaccine oil, oil for FMD biologics, white gidrirovannoe oil, polyalphaolefin oil, polyethylsiloxane liquid, etc.

The quality is impressive, succinimide, emulsifier ARRIAH, APOL product of esterification of a mixture of oleic and stearic acids with polyglycerol and other forming a reverse emulsion type. Oil adjuvant contains 9 parts oil base and 1 part of emulsifier[10, 11, 12, 13, 14]

In izrechenii first included oil adjuvant in the composition of the solvent vistalite, with specified adjuvant along with immunostimulatory activity shows a new, not previously known, the ability to stabilize the conjugate "histamine-polyelectrolyte". Gestalt with oil adjuvant has a higher preventive activity compared with the drug in physiological solution.

Oil adjuvant emuleret with saline solution in a ratio of 1:1.

In the invention, for the first time 3-5% aqueous suspension of silicon dioxide in the composition of the solvent vistalite, while silicon dioxide is showing as part of vistalite immunostimulirutuyu activity. Also discovered a new property of silicon dioxide in the composition of vistalite to stabilize the conjugate "histamine-polyelectrolyte". Gestalt with silicon dioxide has approximately the same preventive activity compared with a preparation containing maricela saline and 3-5% aqueous suspension of silicon dioxide are mixed in equal volumes.

Through the use of a new combination of known and distinctive characteristics of the proposed drug that is achieved technical result consists in increasing the stability of the composition and properties and prophylactic activity of vistalite compared with drug-prototype-gistaglobina, which is confirmed by the results of the research, details of which are given below.

A method for preventing allergological young farm animals includes the following set of essential features that provide technical result, in all cases, which sought the scope of legal protection:

1) use as an antihistamine drug vistalite of the following composition (mg/ml:

Histamine 0,00005 0,0001

Copolymer of vinylpyrrolidone with an organic acid as a carrier - 0,00154 0,0611

The solvent Rest;

2) historic injected animals intramuscularly;

3) historic injected animals single or double;

4) historic administered to animals in a volume of 1-3 ml;

5) Gestalt enter the pigs once for 7-10 days before weaning in the volume of 1-2 ml;

6) Gestalt administered to piglets twice for 14-20 days before weaning with in ml.

Features of the invention describing a method for preventing allergological young farm animals and coinciding with the characteristics of the prototype method, including a generic term that reflects its purpose, are

a method for preventing allergological young farm animals;

use this antihistamine drug.

Compared with the prototype of the salient features of the invention "Method of prevention allergological young farm animals" are:

1) use as an antihistamine drug vistalite of the following composition (mg/ml:

Histamine 0,00005 0,0001

Copolymer of vinylpyrrolidone with an organic acid as a carrier - 0,00154 0,0611

The solvent Rest;

2) historic injected animals intramuscularly;

3) historic injected animals single or double;

4) historic administered to animals in a volume of 1-3 ml;

5) Gestalt enter the pigs once for 7-10 days before weaning in the volume of 1-2 ml;

6) Gestalt administered to piglets twice for 14-20 days before weaning with an interval of 6-8 days in a volume of 2 ml per injection;

7) historic administered to calves in the first d is Oh, the essential distinguishing feature of the proposed method lies in the use of a new antihistamine drug vistalite, is not known. Other distinguishing features of the proposed method, which characterizes the age of the immunized animal, the method, frequency, dosage and timing of administration of the drug to animals cannot be considered in isolation from the distinctive symptom of used drug.

The achievement of the technical result of the invention can be explained by the higher stability of the composition and properties of vistalite and its ability to increase the content of antihistamines factors in the blood of animals, thereby reducing the number of injections of the drug (compared to the prototype) and conduct these operations until weaning piglets and on the first day of life calves.

Through the use of a combination of traits that characterize the proposed method achieved technical result of the invention increase the preventive effect of vistalite and reducing the complexity of its introduction animals.

Example 1. Conjugate "histamine-polymer 1 or 2" is prepared as follows.

When using polymer 1 or 2 is prepared in the Added water-soluble carbodiimide, stirred for 20 min and the pH adjusted to 7.0 by addition of 0.1 M solution of sodium hydroxide or caustic soda, and then poured a 0.1% aqueous solution of histamine dihydrochloride. The mixture is stirred for 72 h at room temperature, then it was added glycine and continue to stir for another 24 h per 1 mol of histamine in response enter 20 mol of water-soluble carbodiimide and 2 or 20 mol of organic acid (acrylic or crotonic) in the composition of the copolymer with vinyl pyrrolidone and 40 mol of glycine after conjugation. Usually conjugate receive in the form of a concentrate containing 100,000 doses in 15 ml. For making a specified number of doses you take 10 mg of histamine dihydrochloride.

Example 2. The composition of gatalica, mg/ml:

Histamine 0,00005

Polymer 1 0,00154

The solvent Else

Conjugate "histamine-polymer 1" is obtained as described in example 1.

As the solvent used saline. For cooking vistalite conjugate dissolved in sterile 0.9% sodium chloride solution pH 7,2-7,4 so that 2 ml of a solution of sodium chloride contained 0.00005 mg of histamine and 0,00154 mg of polymer 1. This amount of the drug is prepared to more accurately dose medication using automatic 3. The composition of gatalica, mg/ml:

Histamine 0,000075

Polymer 1 0.04

The solvent Else

As the solvent used saline. Conjugate "histamine-polymer 1" is obtained as described in example 1.

For cooking vistalite conjugate dissolved in sterile 0.9% sodium chloride solution pH 7,2-7,4 so that 2 ml of a solution of sodium chloride contained 0,000075 mg of histamine and 0.04 mg of polymer 1. Gestalt is transparent with a slight opalescence liquid.

Example 4. The composition of gatalica, mg/ml:

Histamine 0,0001

Polymer 1 0,0611

The solvent Else

Conjugate "histamine-polymer 1" is obtained as described in example 1.

As the solvent used saline.

For cooking vistalite conjugate dissolved in sterile 0.9% sodium chloride solution pH 7,2-7,4 so that 2 ml of a solution of sodium chloride contained 0,0001 mg of histamine and 0,0611 mg of polymer 1. Gestalt is transparent with a slight opalescence liquid.

Example 5. The composition of gatalica, mg/ml:

Histamine 0,00005

Polymer 2 0,00154

The solvent Else

Historic prepared as op is the maker of the Rest

Historic prepared as described in example 3.

Example 7. The composition of gatalica, mg/ml:

Histamine 0,0001

Polymer 2 0,0611

The solvent Else

Historic prepared as described in example 4.

Example 8. The composition of gatalica, mg/ml:

Histamine 0,00005

Polymer 1 0,00154

The solvent Else

Conjugate "histamine-polymer 1" is obtained as described in example 1.

As solvent a mixture of saline solution and oil adjuvant taken in 1:1 ratio.

For cooking vistalite conjugate is first dissolved in sterile 0.9% sodium chloride solution pH 7,2-7,4 so that 0.5 ml of a solution of sodium chloride contained 0.00005 mg of histamine and 0,00154 mg of polymer 1. The resulting solution is mixed with an oil adjuvant at a ratio of 1:1 by dispersing the mixture in a colloid mill for 15 minutes

The resulting Gestalt is a liquid emulsion white.

Example 9. The composition of gatalica, mg/ml:

Histamine 0,000075

Polymer 1 0.04

The solvent Else

Historic prepared as described in example 8. The difference is that the conjugate is dissolved in sterling histamine and 0.04 mg of polymer 1.

Example 10. The composition of gatalica, mg/ml:

Histamine 0,0001

Polymer 1 0,0611

The solvent Else

Historic prepared as described in example 8. The difference is that the conjugate is first dissolved in sterile 0.9% sodium chloride solution pH 7,2-7,4 so that 0.5 ml of a solution of sodium chloride contained 0,0001 mg of histamine and 0,0611 mg of polymer 1.

Example 11. The composition of gatalica, mg/ml:

Histamine 0,00005

Polymer 2 0,00154

The solvent Else

Historic prepared as described in example 8.

Example 12. The composition of gatalica, mg/ml:

Histamine 0,000075

Polymer 2 0.04

The solvent Else

Historic prepared as described in example 9.

Example 13. The composition of gatalica, mg/ml:

Histamine 0,0001

Polymer 2 0,611

The solvent Else

Historic prepared as described in example 10.

Example 14. The composition of gatalica, mg/ml:

Histamine 0,00005

Polymer 1 0,00154

The solvent Else

Conjugate "Gestalt-polymer 2" is obtained as described in example 1.

As solvent a mixture of saline solution and 4% suspension of silicon dioxide pH of 7.2-7.4 in a 1:1 ratio.

For prigot, to 0.5 ml of a solution of sodium chloride contained 0.00005 mg of polymer 1. The resulting solution is mixed with 4% suspension of silicon dioxide pH of 7.2-7.4 in a 1:1 ratio.

Example 15. The composition of gatalica, mg/ml:

Histamine 0,000075

Polymer 1 0.04

The solvent Else

Historic prepared as described in example 14. The difference is that the conjugate is first dissolved in sterile 0.9% sodium chloride solution pH 7,2-7,4 so that 0.5 ml of a solution of sodium chloride contained 0,000075 mg of histamine and 0.04 mg of polymer 1.

Example 16. The composition of gatalica, mg/ml:

Histamine 0,0001

Polymer 1 0,0611

The solvent Else

Historic prepared as described in example 14. The difference is that congat first dissolved in sterile 0.9% sodium chloride solution pH 7,2-7,4 so that 0.5 ml of a solution of sodium chloride contained 0,0001 mg of histamine and 0,0611 mg of polymer 1.

Example 17. The composition of gatalica, mg/ml:

Histamine 0,00005

Polymer 2 0,00154

The solvent Else

Historic prepared as described in example 14.

Example 18. The composition of gatalica, mg/ml:

Histamine 0,000075

Polymer 2 0.04

The solvent Else

Gistel the Polymer 2 0,061

The solvent Else

Historic prepared as described in example 16.

Example 20. Gestalt, obtained as described in example 2, is used for the prevention of oedema disease in piglets. When a single injection of the drug is injected animals intramuscularly for 7-10 days before weaning in the volume of 2 ml, and two for 14-20 days before weaning with an interval of 7 days in a volume of 2 ml for each injection.

The results of the test drug compared to the prototype are given in table. 1.

According to the table. 1 after one or two treatment piglets with gestalta the death of animals from edematous disease were, respectively, 9.0 and 2.6% In that time, after three-time processing of piglets by gistaglobina mortality was 4.7%

Example 21. Historic obtained as described in example 3 is used for the prevention of oedema disease in piglets. The drug is administered to animals as described in example 20.

The test results of vistalite compared with the prototype are given in table. 2.

From table. 2 shows that after one or two treatment piglets with gestalta the death of animals from edematous disease was 6.3 and 1.2% respectively. While, after three injections pigs of gitagovinda mortality was 4.7%
water.

The drug is administered to animals as described in example 20.

The test results of vistalite compared with the prototype are given in table. 3.

From table. 3 shows that the results of testing the effectiveness of prevention edematous disease gestalta prepared in accordance with example 4, similar to the results shown in table 2.

Example 23.

Gestalt, obtained as described in example 5 is used for the prevention of oedema disease in piglets.

The drug is administered to animals as described in example 20.

The results of the test drug compared to the prototype are given in table. 4.

From table. 4 shows that the results of the application of gatalica, obtained as described in example 5 does not differ from the test results of gatalica, prepared as described in example 2.

Example 24. Gestalt, obtained as described in example 6, is used for the prevention of oedema disease in piglets.

The drug is administered to animals as described in example 20.

The results of the test drug compared to the prototype are given in table. 5.

From table. 5 it follows that the mortality of piglets from edematous disease after single and the AK, as described in example 7, is used for the prevention of oedema disease in piglets.

The drug is administered to animals as described in example 20.

The results of the test of the drug in comparison with the prototype are given in table. 6.

From table. 6 shows that the results of the prevention of edema disease of pigs by gestalta, prepared as described in example 7, were similar to the results disclosed in example 24.

Example 26. Gestalt, obtained as described in example 8, is used for the prevention of oedema disease in piglets.

The drug is injected animals intramuscularly for 7-10 days before weaning in a volume of 1 ml in a single dose.

The results of the test drug compared to the prototype are given in table. 7.

According to the table. 7 after a single treatment of piglets with gestalta the death of animals from edematous disease was 4.0%

Princr 27. Gestalt, obtained as described in example 9, is used for the preventive treatment of oedema disease in piglets.

The drug is administered to animals as described in example 26.

The test results of vistalite compared with the prototype are given in table. 8.

Analyzing the data table. 8, it can be concluded that the mortality of parola to lower case.

Example 28. Gestalt, obtained as described in example 10, is used for the preventive treatment of oedema disease in piglets.

The drug is administered to animals as described in example 26.

The results of the test drug compared to the prototype are given in table. 9.

From table. 9 shows that the mortality of piglets from edematous disease after a single treatment gestalta was excluded.

Example 29. Gestalt, obtained as described in examples 8 or 11, is used for the prevention of oedema disease in piglets.

The drug is administered to animals as described in example 26.

The test results of vistalite compared with the prototype are given in table. 10.

From table. 10 shows that the results of processing piglets with gestalta for the prevention of edema disease were similar to the results described in example 26.

Example 30. Gestalt, obtained as described in examples 9 or 12, is used for the prevention of oedema disease in piglets.

The drug is administered to animals as described in example 26.

The results of the test drug compared to the prototype held in the table. 11.

From table. 11 it follows that the results of the prevention swollen bolty so, as described in examples 10 and 13, are used for the prevention of edema disease of swine.

The drug is administered to animals as described in example 26.

The results of the test drug compared to the prototype held in the table. 12.

From table. 12 shows that the mortality of piglets from edematous disease after treatment with gestalta was equal to 1% of

Example 32. Gestalt, obtained as described in example 14, is used for the prevention of oedema disease in piglets.

The drug is administered to animals as described in example 26.

The test results of vistalite compared with the prototype are given in table. 13.

From table. 13 it follows that the mortality of piglets from edematous disease after prophylaxis gestalta after a single treatment accounted for 5.0%

Example 33. Gestalt, obtained as described in example 15, are used for the prevention of edema disease of swine.

The drug is administered to animals as described in example 26.

The test results of vistalite compared with the prototype are given in table. 14.

From table. 14 shows that after a single treatment of piglets with gestalta, deaths from edematous disease was equal to 0.6%

Example 34. Historic obtained as ω so that as described in example 26.

The test results of vistalite compared with the prototype are given in table. 15.

According to the table. 15 the mortality of piglets from edematous disease after a single treatment with gestalta was 1%

Example 35. Gestalt, obtained as described in examples 14 or 17, is used for the prevention of oedema disease in piglets.

The drug is administered to animals as described in example 26.

The test results of vistalite compared with the prototype are given in table. 16.

From table. 16 shows that the results of the processing of piglets by gestalta for the prevention of edema disease were similar to the data given in example 32.

Example 36. Gestalt, obtained as described in examples 15 and 18, are used for the prevention of edema disease of swine.

The drug is administered to animals as described in example 26.

The test results of vistalite compared with the prototype are given in table. 17.

From table. 17 it follows that the mortality of piglets from edema disease in the first group was equal to 0.6%

Example 37. Gestalt, obtained as described in examples 16 and 19, are used for the prevention of edema disease of swine.

The drug entering shown in table. 18.

From table. 18 shows that after treatment of piglets with gestalta once the case from edematous disease was 1%

Example 38. In experiments on laboratory animals (white mice weighing 16 18 g) was tested for acute toxicity and local (skin) reaction by the introduction of free histamine and its conjugates. The research results are summarized in table. 19.

Presented in table. 19 the results indicate that historic and listglobal not called as a local shared reactions. While histamine as part of vistalite was introduced in 44 times more than in the composition of gitagovinda (administration of higher doses of the prototype is technically impossible). At the same time, the introduction of free histamine in the same dose caused a local reaction, which manifests itself in the form of swelling, redness tissue and changes in General condition, resembling anaphylactic shock.

Thus it is shown that Gestalt is non-toxic drug. Therefore, it contains histamine securely immobilisation.

Example 39. In a series of experiments investigated the effects of media histamine on the expression of the protective activity of antihistamines. This formed 5 groups of piglets in vozraste. 20 the results show that among the pigs of the control group edema disease struck 3.3% of the animals despite the fact that within 20 Nam, after weaning of piglets in this group were held on a semi-starvation diet. At the same time in group 4 (experimental), in which the animals were kept on a semi-starvation diet for 7-10 Nam, ill fewer piglets. When used as a carrier of gamma-globulin (alcohol) and polymer 1, the incidence was 0.7% which is substantially lower than in the control group. When used as a carrier BSA protective effect was absent. Thus, the polymer 1 was found to be an effective media when creating an antihistamine drug.

Example 40. In a series of experiments we studied the efficiency of sample vistalite-based polymer 1, but with different histamine load. With the same content, the number of polymer 1 in the drug And was 10 times more than the drug Century. While the total dose of histamine in pravilnoy dose of 0.2 mg of histamine dihydrochloride. The results are shown in table. 21.

Presented in table. 21 data shows that when using vistalite "high load of histamine" (group b) protective effi which she had fallen.

Based on these data in future work used Gestalt with polymer 1 containing one pravilnoy dose of 0.2 mg of histamine dihydrochloride in the composition of the conjugate.

Example 41. 7-10 days before weaning piglets were treated once at a volume of 1 ml gestalta with polymer 2, which contained 0.2 ág histamine dihydrochloride at a ratio of histamine: polymer 2, which is 1:2. A similar group was left as control for observation. The research results are summarized in table.22.

Presented in table. 22 the results show that Gestalt has provided not only a reduction of incidence in the experimental group by 4.2% compared with the control, but allowed to move from a semi-starvation diet for complete feeding on 18 Nam, which guarantees the best overall development of piglets and large gain.

Example 42. Because allergic reactions play a role in pneumoenteritis (neuralgia, pneumonia) calves were experiments on the use of vistalite for the prevention of these diseases.

To determine the effectiveness of vistalite as a means of preventing pneumoenteritis calves affected with this disease sector were set up shop data the globin dose of 1,2 and 3 ml (aged 1,4 and 7 days), the calves of the second group Gestalt on the first day of life in a volume of 2-3 ml of the Same group remained under the supervision of the quality control. The animals were observed for 21 Nam, recording the incidence, the amount of hemoglobin in the blood and General immunological response (FID) intradermal reaction by Ioffe. The research results are summarized in table. 23.

Set in the table. 23 evidence suggests that after gitagovinda and vistalite the incidence of calves decreased by 50% In calves of the experimental group increased the content of hemoglobin in the blood, whereas animals in the control group the number of hemoglobin in blood samples decreased. In addition, when determining the FID in response to the introduction individuai serum increased skin folds more than 0.6 mm

Thus, Gestalt is not inferior in its activity the prototype. The authors suggest an antihistamine Gestalt and a method for preventing allergological in young farm animals using vistalite provides prototyping the following benefits:

historic exhibits a noticeable anti-allergic activity and provides pronounced proindustrial, since the conjugation histamine polymers 1 and 2 occurs at specific physico-chemical parameters and on the device itself, not antibodies;

the cost of the polymers 1 and 2 below cost gamma globulin;

reducing the complexity of the introduction of vistalite.

Gestalt and a method for preventing allergological young farm animals using vistalite will find application in agricultural production to prevent edema disease of pigs and pneumoenteritis calves.

Source of information:

1. Prokhorov F. F. Edema disease of pigs. (Etiology, symptoms and signs, treatment). Veterinary medicine, 1984, 8, 36-38.

2. Matushev P.F. Activities against edema disease (kolienterotoxemia) pigs. Veterinary medicine, 1994, 4, 9-13.

3. Eremeev, M. N. About the pathogenicity of Escherichia coli allocated when the swollen bolezni piglets. Veterinary medicine, 1971, 2, 52-53.

4. Matushev P.F. Prevention of edema disease of swine. Veterinary medicine, 1985, 7, 38-39.

5. Matushev P.F. Prevention of oedema disease in piglets. Veterinary medicine, 1973, 3, 62-63 (prototype).

6. Petrov R. C. Immune biotechnology: achievements and prospects. GWHO them. D. I. Mendeleev, 1988, XXXIII, 5, 484-493.

8. Starlings C. Y. Masternak T. B. and others, the Study of immunomodulatory and toxic characteristics of the copolymers of vinylpyrrolidone with crotonic acid and vinylamine. Immunology, 1989, 3, 63-65.

9. Bed, M "Owls.Encyclopedia", 1978, ed. 3, T. 9, S. 57.

10. Foot and mouth disease. Burdov A. N. Dudnikov A. I. Malaret P. C., and others/edited by A. N. Burdova. M Agropromizdat, 1990, 239-250.

11. RF patent N 1615917, class A 61 K 39/135, 35/06; 10.05.89.

12. RF patent N 1615918, class A 61 K 39/135, 35/06; 22.05.89.

13. RF patent N 1692022, class A 61 K 39/135, 35/06; 31/23. 30.11.89.

14. RF patent N 1743027, class A 61 K 39/135, 35/06; 30.11.89.

1. An antihistamine containing histamine, its medium and a solvent, characterized in that as the carrier of the drug contains a copolymer of vinylpyrrolidone with an organic acid in the following ratio of ingredients, in mg/ml:

Histamine 0,00005 0,0001

Copolymer of vinylpyrrolidone with an organic acid 0,00154 0,00611

The solvent Else

2. The drug under item 1, characterized in that as the carrier of the drug contains a copolymer of vinylpyrrolidone and acrylic acid.

3. The drug under item 1, characterized in that as the carrier of the drug contains a copolymer of vinylpyrrolidone with crotonic acid is a great solution.

5. The drug under item 1, characterized in that the solvent of the drug contains a mixture of saline solution and oil adjuvant in the ratio of 1 to 1.

6. The drug under item 1, characterized in that the solvent of the drug contains a mixture of saline and 3 5% aqueous suspension of silicon dioxide in a ratio of 1 to 1.

7. A method for preventing allergological young farm animals, including medication, characterized in that as an antihistamine drug used Gestalt of the following composition (mg/ml:

Histamine 0,00005 0,0001

Copolymer of vinylpyrrolidone with an organic acid 0,00154 0,0611

The solvent Else

which is injected animals intramuscularly one or twice with an interval of 6 to 8 days in the amount of 1 to 3 ml per injection.

8. The method according to p. 7, characterized in that Gestalt enter the pigs once for 7 to 10 days before weaning in the amount of 1 2 ml.

9. The method according to p. 7, characterized in that historic administered to piglets twice for 14 to 20 days before weaning at intervals of 6 to 8 days in the amount of 1 to 2 ml per injection.

10. The method according to p. 9, characterized in that historic administered to calves in the

 

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